Nobel Prize winner Dr. Judah Folkman first proposed in 1971 that all cancer tumors were angiogenesis-dependent and therefore targeting angiogenesis was a potential means for treating cancer. Angiogenesis is the growth of new capillaries from pre-existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, are associated with either excessive or deficient angiogenesis.
It is now widely accepted that tumor growth beyond a few cubic millimeters cannot occur without the induction of a new vascular supply. Therefore, inhibition of new vasculature (antiangiognesis) can provide a non-chemotherapy or non-radiation therapy approach to the treatment of cancer by denying tumors the nutrient supply necessary for the tumors to grow. Although normally quiescent, endothelial cells are responsible for the formation of new vasculature in response to various stimuli. These stimuli can have their genesis in many forms.
The endothelial cells which form new vascular networks in tumors respond to angiogenic stimuli produced by the tumor itself. The best known of these stimuli is vascular endothelial growth factor (VEGF). Found to be ubiquitous in human tumors, increasing levels of VEGF correlate with an increasing rate of tumor growth. Therefore, suppression of VEGF represents a method for controlling the growth rate of tumors (primary and metastatic) and offers a possible means for shrinking existing tumors.
Therefore, there is a long felt need for compounds, compositions, and methods for suppressing VEGF expression by tumor cells.